Spontaneous fibrous lesions which arise in the arteries of man and experimental animals appear to be precursors of atherosclerotic plaques. In cockerel aortas such as lesions are present by 4 weeks of age. In control birds lesions growth is slow until 20 weeks of age and then levels off. Weekly injections of polycyclic aromatic hydrocarbon carcinogens (PAHC) starting at 4 weeks of age result in increased proliferation and accelerated size increases of these lesions without any increase in lesion number. The size increases are most pronounced when the birds reach full size. Continued PAHC exposure is needed for the increases. Thus, in this system PAHC promote lesion development rather than initiate new lesions. We seek to understand how these agents interact with the arterial system and what steps are involved in growth and development of spontaneous lesions. We will study the kinetics of labeled cells to learn whether lesion cells responsive to PAHC are derived from a pool of non-dividing cells. Ultrastructural and biochemical methods will be used to learn whether PAHC cause endothelial damage. We will screen other environmental agents for atherogenic potential. We will test whether cholesterol feeding exacerbates lesion development and whether active protease inhibitors, retinyl acetate or aspirin added to the diet interfere with lesion development. Localization of PAHC within lesion cells, biochemical activation of PAHC by these cells and alterations in patterns and levels of protein synthesis associated with lesion formation will be studied. Methods for isolation of large numbers of single cells from lesions and from the artery wall will be developed. These studies will provide valuable information regarding the promotional nature of carcinogens; the early steps and processes associated with growth and development of spontaneous lesions; and, the capacity of environmental factors including pollutants and dietary supplements to modify the process of atherosclerotic plaque formation.